The primary objective of this project is the study of the mechanism of brain involvement and mental retardation in the patients with mucopolysaccharidoses (MPS). We are using a comparative approach. For this purpose, whole brain, brain gray and white matter, brain cells and other fractions and tissues from patients with MPS IH, MPS IS (this patient was of normal intelligence), MPS II, MPS IIIA, and MPS IIIB and from non-neurological patients are examined for glycosaminoglycans, sphingolipids and lysosomal enzymes. To complement the studies with human subjects, an animal model of mucopolysaccharidosis is being developed. The drug suramin given intravenously and intracerebrally to rats inhibits enzymes of glycosaminoglycan degradation and causes accumulation of glycosaminoglycans and sphingolipids in the tissues.